Inclisiran (Leqvio – Novartis), a subcutaneously injected small interfering RNA (siRNA) that decreases LDL-cholesterol (LDL-C) levels by reducing synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9), has been approved by the FDA for use with or without a statin to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Inclisiran had previously been approved for use only in combination with statin therapy.

The oral adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid was approved by the FDA in 2020 for use alone (Nexletol – Esperion) and in a fixed-dose combination with the cholesterol absorption inhibitor ezetimibe (Nexlizet) as an adjunct to maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-cholesterol (LDL-C) lowering. The indication has now been expanded to include reducing the risk of myocardial infarction (MI) and coronary...

Since our initial review of the oral lipid-lowering adenosine triphosphate-citrate lyase (ACL) inhibitor bempedoic acid (Nexletol – Esperion) in 2020, cardiovascular outcomes data in statin-intolerant patients have become available.

The FDA has approved inclisiran (Leqvio – Novartis), a small interfering RNA (siRNA) directed to proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA, as an adjunct to diet and maximally tolerated statin therapy for subcutaneous (SC) treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Inclisiran is the first FDA-approved PCSK9-directed siRNA therapeutic agent.

The FDA has approved changes to the wording of the cardiovascular risk reduction indications for the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab (Repatha) and alirocumab (Praluent). Both drugs are now approved to reduce the risk of major adverse cardiovascular events (MACE) in adults at increased risk for these events; they were previously approved to reduce the risk of MACE only in patients with established cardiovascular disease (CVD).

View the Comparison Chart: Some Non-Statin Lipid-Lowering Drugs

The FDA has approved lerodalcibep (Lerochol – Lib Therapeutics), a subcutaneously injected proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Lerodalcibep is the fourth subcutaneously injected PCSK9-directed therapy to be approved in the US; the monoclonal antibodies alirocumab (Praluent) and evolocumab (Repatha) and the small interfering RNA inclisiran (Leqvio) were approved earlier (see Table...

View the Comparison Table: Some Lipid-Lowering Drugs

Recently published multisociety guidelines for the management of dyslipidemia emphasize early identification and treatment of dyslipidemia to reduce the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) and death.

Cholesterol management guidelines from the American College of Cardiology/American Heart Association Task Force were last published in 2019.